Foods that are rich in advanced glycation end products (AGEs) from high cooking temperatures - including fried and cooked meats - may increase the risk of developing dementia, according to new research.

The findings, published in PNAS, suggest that compounds known as advanced glycation endproducts (AGE's) may be one possible cause of the accumulation of amyloid plaques that are characteristic of dementia and Alzheimer’s disease progression.

Led by senior author Professor Helen Vlassara from The Mount Sinai Hospital in the US, the research team tested the effect of AGEs on mice and people - finding that that mice fed a high-AGE diet had a build-up of amyloid proteins in the brain and impaired cognitive function, while those eating a low-AGE diet had no amyloid build up.

Furthermore, a short-term analysis of humans also suggested a link between high levels of AGEs in the blood and cognitive decline, said Vlassara and her team.

"These clinical findings reinforce the fact that chronic exposure to exogenous AGEs can weaken host defences well in advance of cognitive or metabolic disturbances," said the team.

The fact that mice fed a low-AGE diet had no build of amyloid protein or cognitive decline highlights the fact that such 'glycotoxins' are a modifiable risk for Alzheimer's disease, they added.

"Age-related dementia and metabolic syndrome may be causally linked to high levels of food AGEs, specifically MG [methyl-glyoxal derivatives]," concluded Vlassara and her colleagues.

"Importantly, reduction of food-derived AGES is feasible and may provide an effective treatment strategy," they added.

AGE related diseases?

The researchers noted that AGEs are present in a wide variety of foods in the Western diet and have previously been linked to diabetes and to neurodegenerative disease. Indeed, AGEs have been linked to dementia when present in the bloodstream and the brain at high levels, however the mechanism behind the link is largely unknown, they said.

Previous research published in the International Journal of Food Sciences and Nutrition has also linked AGEs to the formation of a plaques
, however in this case it was the formation of plaques associated with cardiovascular disease.

Study details

In the first part of their study, the team tracked cognitive health in mice that were fed one of three diets containing various levels of AGEs at levels proportional to a Western diet: low-AGE (MG−), MG-supplemented low-AGE (MG+), and a regular (Reg) chow that is higher in ACEs and methyl-glyoxal derivatives (MG).

The team found that older MG+-fed mice, similar to older regular fed controls, developed metabolic syndrome, increased brain amyloid-beta, deposits of AGEs, gliosis, and cognitive deficits, accompanied by suppressed SIRT1, nicotinamide phosphoribosyltransferase, AGE receptor 1, and PPAR-gamma.

"These changes were not due to aging or caloric intake, as neither these changes nor the MS were present in age-matched, pair-fed MG− mice," said the team.

In a follow-on clinical study of 93 healthy humans over the age of 60, the team also found that individuals who had high AGEs in their blood also had low SIRT1 levels in their blood and developed cognitive decline and insulin resistance over a nine month follow-up period.

"The data identify a specific AGE (MG) as a modifiable risk factor for AD and MS, possibly acting via suppressed SIRT1 and other host defenses, to promote chronic oxidant stress and inflammation," concluded Vlassara and her colleagues.

"Because SIRT1 deficiency in humans is both preventable and reversible by AGE reduction, a therapeutic strategy that includes AGE reduction may offer a new strategy to combat the epidemics of AD and MS."
Source: PNAS
Published online ahead of print, doi: 10.1073/pnas.1316013111"Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans"Authors: Weijing Cai, Jaime Uribarri, et al

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Foods that are rich in advanced glycation end products (AGEs) from high cooking temperatures - including fried and cooked meats - may increase the risk of developing dementia, according to new research.